Dendritic Mechanisms Underlying Behaviorally-Relevant Activity in a Descending Auditory Pathway

Project Summary/Abstract
Active listening is central to auditory cognition, supporting critical functions such as stream segregation,
linguistic analysis and perceptual learning. To this end, the brain must accurately represent the physical
properties of acoustic signals and subsequently parse sounds based on their behavioral relevance. Whereas
the encoding of primary features such as amplitude and spectral content typically begins in specialized
brainstem and midbrain circuits, the mechanisms by which sounds attain behavioral relevance are poorly
understood. A long-standing assumption is that descending projections from auditory cortex, which contact
most early ascending auditory circuits, play a critical role in ascribing behavioral relevance to sounds. Indeed,
descending auditory cortical projections could provide an anatomical substrate for "top-down" signals to control
the "bottom-up" encoding of acoustic features. Despite this presumed importance, little is known about the
function of descending auditory cortical neurons in attentive listening, nor do we understand the biophysical
mechanisms that dictate their contribution to central auditory processing. Our goal is to address these
knowledge gaps in behaving mice by studying the descending pathway from auditory cortex to inferior
colliculus, an auditory midbrain region critical for perceiving complex sounds. Our unpublished results support
a working hypothesis whereby auditory cortico-collicular neurons encode learned information, thereby
transmitting signals that amplify the representation of behaviorally relevant sound features in early auditory
circuits. Our data further suggest that a key mechanism underlying the activity of auditory cortico-collicular
neurons during active listening is the non-linear generation of dendritic spikes, powerful electrical events that
initiate in the apical dendrites of cortical neurons and drive high-frequency burst firing at the soma. We propose
testing these hypotheses using a unique combination of sub-cellular 2-photon Ca2+ imaging, optogenetics and
behavioral assays in awake, head-fixed mice. The positive outcome will be to establish functional and
mechanistic answers for the operation of a descending auditory cortical pathway during attentive listening,
thereby shedding light on a critical yet poorly understood facet of the central auditory system.

Grant Number: 3R01DC019090-05S1
NIH Institute/Center: NIH
Principal Investigator: Pierre Apostolides